tbuckley/cabot-search huggingface dataset:
<i>ACTA2</i>Expression Predicts Survival and Is Associated with Response to Immune Checkpoint Inhibitors in Gastric Cancer
Authors: Sunho Park, John D. Karalis, Changjin Hong, Jean R. Clemenceau, Matthew R. Porembka, In-Ho Kim, Sung Hak Lee, Sam C. Wang, Jae-Ho Cheong, Tae Hyun Hwang
Journal: Clinical Cancer Research (2022)

We sought to identify biomarkers that predict overall survival (OS) and response to immune checkpoint inhibitors (ICI) for patients with gastric cancer.This was a retrospective study of multiple independent cohorts of patients with gastric cancer. The association between tumor ACTA2 expression and OS and ICI response were determined in patients whose tumors were analyzed with bulk mRNA sequencing. Single-cell RNA sequencing (scRNA-seq) and digital spatial profiling data were used to compare tumors from patients with gastric cancer who did and did not respond to ICI.Increasing tumor ACTA2 expression was independently associated with worse OS in a 567-patient discovery cohort [HR, 1.28 per unit increase; 95% confidence interval (CI), 1.02-1.62]. This finding was validated in three independent cohorts (n = 974; HR, 1.52 per unit increase; 95% CI, 1.34-1.73). Of the 108 patients treated with ICI, 56% of patients with low ACTA2 expression responded to ICI versus 25% of patients with high ACTA2 expression (P = 0.004). In an analysis of a publicly available scRNA-seq dataset of 5 microsatellite instability-high patients treated with ICI, the patient who responded to ICI had lower tumor stromal ACTA2 expression than the 4 nonresponders. Digital spatial profiling of tumor samples from 4 ICI responders and 5 ICI nonresponders revealed that responders may have lower ACTA2 expression in α-SMA-positive cancer-associated fibroblasts (CAF) than nonresponders (median: 5.00 vs. 5.50).ACTA2 expression is associated with survival and ICI response in patients with gastric cancer. ACTA2 expression in CAFs, but not in other cellular compartments, appears to be associated with ICI response.
Scaffold‐Free Tracheal Engineering via a Modular Strategy Based on Cartilage and Epithelium Sheets
Authors: Minglei Yang, Jiafei Chen, Yi Chen, Weikang Lin, Hai Tang, Ziwen Fan, Long Wang, Yunlang She, Feng Jin, Lei Zhang, Weiyan Sun, Chang Chen
Journal: Advanced Healthcare Materials (2022)

Tracheal defects lead to devastating problems, and practical clinical substitutes that have complex functional structures and can avoid adverse influences from exogenous bioscaffolds are lacking. Herein, a modular strategy for scaffold-free tracheal engineering is developed. A cartilage sheet (Cart-S) prepared by high-density culture is laminated and reshaped to construct a cartilage tube as the main load-bearing structure in which the chondrocytes exhibit a stable phenotype and secreted considerable cartilage-specific matrix, presenting a native-like grid arrangement. To further build a tracheal epithelial barrier, a temperature-sensitive technique is used to construct the monolayer epithelium sheet (Epi-S), in which the airway epithelial cells present integrated tight junctions, good transepithelial electrical resistance, and favorable ciliary differentiation capability. Epi-S can be integrally transferred to inner wall of cartilage tube, forming a scaffold-free complex tracheal substitute (SC-trachea). Interestingly, when Epi-S is attached to the cartilage surface, epithelium-specific gene expression is significantly enhanced. SC-trachea establishes abundant blood supply via heterotopic vascularization and then is pedicle transplanted for tracheal reconstruction, achieving 83.3% survival outcomes in rabbit models. Notably, the scaffold-free engineered trachea simultaneously satisfies sufficient mechanical properties and barrier function due to its matrix-rich cartilage structure and well-differentiated ciliated epithelium, demonstrating great clinical potential for long-segmental tracheal reconstruction.
<i>Lactococcus lactis</i>‐derived microparticles <i>ad mixed</i> with allergen shift immune responses towards a regulatory profile in tree‐nut allergic patients
Authors: Francisca Palomares, Cristobalina Mayorga, Kees Leenhouts, Natalia Perez‐Sanchez, Francisca Gomez, Maria Jose Torres, Poul Sørensen
Journal: Allergy (2022)
Contextual Considerations When Interpreting Well-Child Visit Adherence Results
Authors: Sarah L. Goff
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Evaluation of a real-time computer-aided polyp detection system during screening colonoscopy: AI-DETECT study
Authors: Ahmir Ahmad, Ana Wilson, Adam Haycock, Adam Humphries, Kevin Monahan, Noriko Suzuki, Siwan Thomas-Gibson, Margaret Vance, Paul Bassett, Kowshika Thiruvilangam, Angad Dhillon, Brian P. Saunders
Journal: Endoscopy (2022)

Abstract Background Polyp detection and resection during colonoscopy significantly reduce long-term colorectal cancer risk. Computer-aided detection (CADe) may increase polyp identification but has undergone limited clinical evaluation. Our aim was to assess the effectiveness of CADe at colonoscopy within a bowel cancer screening program (BCSP). Methods This prospective, randomized controlled trial involved all eight screening-accredited colonoscopists at an English National Health Service (NHS) BCSP center (February 2020 to December 2021). Patients were randomized to CADe or standard colonoscopy. Patients meeting NHS criteria for bowel cancer screening were included. The primary outcome of interest was polyp detection rate (PDR). Results 658 patients were invited and 44 were excluded. A total of 614 patients were randomized to CADe (n = 308) or standard colonoscopy (n = 306); 35 cases were excluded from the per-protocol analysis due to poor bowel preparation (n = 10), an incomplete procedure (n = 24), or a data issue (n = 1). Endocuff Vision was frequently used and evenly distributed (71.7 % CADe and 69.2 % standard). On intention-to-treat (ITT) analysis, there was a borderline significant difference in PDR (85.7 % vs. 79.7 %; P = 0.05) but no significant difference in adenoma detection rate (ADR; 71.4 % vs. 65.0 %; P = 0.09) for CADe vs. standard groups, respectively. On per-protocol analysis, no significant difference was observed in these rates. There was no significant difference in procedure times. Conclusions In high-performing colonoscopists in a BCSP who routinely used Endocuff Vision, CADe improved PDR but not ADR. CADe appeared to have limited benefit in a BCSP setting where procedures are performed by experienced colonoscopists.
A self-fused hydrogel for the treatment of glottic insufficiency through outstanding durability, extracellular matrix-inducing bioactivity and function preservation
Authors: Chen-Yu Zou, Juan-Juan Hu, Dan Lu, Qian-Jin Li, Yan-Lin Jiang, Rui Wang, Hai-Yang Wang, Xiong-Xin Lei, Jesse Li-Ling, Hui Yang, Hui-Qi Xie
Journal: Bioactive Materials (2022)

Injection laryngoplasty with biomaterials is an effective technique to treat glottic insufficiency. However, the inadequate durability, deficient pro-secretion of extracellular matrix (ECM) and poor functional preservation of current biomaterials have yielded an unsatisfactory therapeutic effect. Herein, a self-fusing bioactive hydrogel comprising modified carboxymethyl chitosan and sodium alginate is developed through a dual-crosslinking mechanism (photo-triggered and dynamic covalent bonds). Owing to its characteristic networks, the synergistic effect of the hydrogel for vocal folds (VFs) vibration and phonation is adequately demonstrated. Notably, owing to its inherent bioactivity of polysaccharides, the hydrogel could significantly enhance the secretion of major components (type I/III collagen and elastin) in the lamina propria of the VFs both
The Epitope Basis of Embryonic Stem Cell‐Induced Antitumor Immunity against Bladder Cancer
Authors: Meiling Jin, Jingchu Hu, Lili Tong, Bao‐Zhong Zhang, Jian‐Dong Huang
Journal: Advanced Healthcare Materials (2022)

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) share many cellular and molecular features with cancer cells. Taking advantage of these similarities, stem cells are effective vaccines against cancers in animal models. However, the molecular basis is not well understood, which hinders the development of effective cancer vaccines. Here, prophylactic and therapeutic bladder cancer vaccines composed of allogeneic ESCs and CpG with or without granulocyte macrophage colony stimulating factor are tested. The ESC-based cancer vaccines are able to induce specific antitumor immunity including stimulating cytotoxic CD8
GLUT-1/PKM2 loop dysregulation in patients with non-ST-segment elevation myocardial infarction promotes metainflammation
Authors: Francesco Canonico, Daniela Pedicino, Anna Severino, Ramona Vinci, Davide Flego, Eugenia Pisano, Alessia d’Aiello, Pellegrino Ciampi, Myriana Ponzo, Alice Bonanni, Astrid De Ciutiis, Sara Russo, Marianna Di Sario, Giulia Angelini, Piotr Szczepaniak, Alfonso Baldi, Boguslaw Kapelak, Karol Wierzbicki, Rocco A Montone, Domenico D’Amario, Massimo Massetti, Tomasz J Guzik, Filippo Crea, Giovanna Liuzzo
Journal: Cardiovascular Research (2022)

Abstract Aims The functional capacity of the immune cells is strongly dependent on their metabolic state and inflammatory responses are characterized by a greater use of glucose in immune cells. This study is aimed to establish the role of glucose metabolism and its players [glucose transporter 1 (GLUT-1) and pyruvate kinase isozyme M2 (PKM2)] in the dysregulation of adaptive immunity and inflammation observed in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Methods and results We enrolled 248 patients allocated to three groups: NSTEMI patients, chronic coronary syndromes (CCS) patients, healthy subjects (HSs). NSTEMI patients showed higher expression of GLUT-1 and an enhanced glucose uptake in T cells when compared with CCS patients (P &amp;lt; 0.0001; P = 0.0101, respectively) and HSs (P = 0.0071; P = 0.0122, respectively). PKM2 had a prevalent nuclear localization in T lymphocytes in NSTEMI (P = 0.0005 for nuclear vs. cytoplasm localization), while in CCS and HS, it was equally distributed in both compartments. In addition, the nuclear fraction of PKM2 was significantly higher in NSTEMI compared with HS (P = 0.0023). In NSTEMI patients, treatment with Shikonin and Fasentin, which inhibits PKM2 enzyme activity and GLUT-1-mediated glucose internalization, respectively, led to a significant reduction in GLUT-1 expression along with the down-regulation of pro-inflammatory cytokine expression. Conclusion NSTEMI patients exhibit dysregulation of the GLUT-1/PKM2 metabolic loop characterized by nuclear translocation of PKM2, where it acts as a transcription regulator of pro-inflammatory genes. This detrimental loop might represent a new therapeutic target for personalized medicine.
β-Defensin 19/119 mediates sperm chemotaxis and is associated with idiopathic infertility
Authors: Xiaofeng Li, Chun Yuan, Jianwu Shi, Hang Kang, Yufei Chen, Yonggang Duan, Jing Jin, Lai Ping Cheung, Tin Chiu Li, Ying Liu, Yugui Cui, Ye Chun Ruan, Xiaohua Jiang, Zhiming Cai, Hsiao Chang Chan, Ling Ji, Xuhui Zeng, Jiaying Liu, Hao Chen, Kin Lam Fok
Journal: Cell Reports Medicine (2022)
circCYP24A1 facilitates esophageal squamous cell carcinoma progression through binding PKM2 to regulate NF-κB-induced CCL5 secretion
Authors: Lina Gu, Yang Sang, Xixi Nan, Yang Zheng, Fei Liu, Lingjiao Meng, Meixiang Sang, Baoen Shan
Journal: Molecular Cancer (2022)

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal malignant tumor, while the molecular mechanisms have not been fully elucidated. Multiple circular RNAs have been reported to involve in the onset and progression of malignant tumors through various molecular mechanisms. However, the clinical significance and functional mechanism of most circRNAs involved in the progression of ESCC remains obscure. Methods RNA-Seq was used to explore potential circRNAs in participated in 5 pairs of ESCC and their corresponding normal esophageal tissues. The up-regulated circCYP24A1 was selected. Fluorescence in situ hybridization was cunducted to verificated the expression and intracellular localization of circCYP24A1 by using the tissue microarray. The Kaplan–Meier method and Cox proportional hazards model was used to examine the potential prognostic value of circCYP24A1 on overall survival of ESCC patients. The biological function were confirmed by gain- and loss-of-function approaches in vivo. mRNA expression profile microarray was proformed to investigate the downstream signaling pathways involved in circCYP24A1. RNA pull-down assay and mass spectrometry were performed to identify the proteins associated with circCYP24A1. Rescue experiments were carried out to identified hypothetical regulatory role of circCYP24A1 on ESCC progression in vivo and in virto. Results In this study, we identified circCYP24A1 in ESCC tissues by RNA sequencing, which is up-regulated in 114 cases of ESCC tissues and acts as a novel prognosis-related factor. Moreover, circCYP24A1 promoted the ability of proliferation, migration, invasion and clone formation in vitro, as well as tumor growth in vivo. Mechanistically, chemokine (C-Cmotif) ligand 5 (CCL5) is functional downstream mediator for circCYP24A1, which is screened by mRNA microarray. Moreover, circCYP24A1 physically interacts with M2 isoform of pyruvate kinase (PKM2). Rescue experiments showed that PKM2 knockdown partly reverses the promotional effects of circCYP24A1. It was revealed that circCYP24A1 increases secretion of CCL5 through the mechanism mainly by interacting with PKM2, an activator of NF-κB pathway, and thereby accelerate malignant progression of ESCC. Conclusions Up-regulated circCYP24A1 could activate NF-κB pathway by binding PKM2, which promotes the secretion of CCL5 and accelerate malignant progression of ESCC. Our fndings recommended a novel function for circCYP24A1 as a potential effective biomarker for judging prognosis and a therapeutic target in ESCC.
Lanadelumab for the prevention of hereditary angioedema attacks: A real‐world <scp>UK</scp> audit
Authors: Anthony D. Dorr, Charu Chopra, Tanya I. Coulter, John Dempster, Magdalena Dziadzio, Tariq El‐Shanawany, Tomaz Garcez, Mark Gompels, Richard Herriot, Rashmi Jain, Marcel Levi, Lorena Lorenzo, Inas Makki, Elizabeth Mapazire, Sai H. K. Murng, Sadia Noorani, Sinisa Savic, Cathal L. Steele, Christine Symons, Michael Tarzi, Patrick F. K. Yong, Sorena Kiani‐Alikhan
Journal: Allergy (2022)

Appendix S1: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Exome-wide association analysis of CT imaging-derived hepatic fat in a medical biobank
Authors: Joseph Park, Matthew T. MacLean, Anastasia M. Lucas, Drew A. Torigian, Carolin V. Schneider, Tess Cherlin, Brenda Xiao, Jason E. Miller, Yuki Bradford, Renae L. Judy, Anurag Verma, Scott M. Damrauer, Marylyn D. Ritchie, Walter R. Witschey, Daniel J. Rader
Journal: Cell Reports Medicine (2022)

Nonalcoholic fatty liver disease is common and highly heritable. Genetic studies of hepatic fat have not sufficiently addressed non-European and rare variants. In a medical biobank, we quantitate hepatic fat from clinical computed tomography (CT) scans via deep learning in 10,283 participants with whole-exome sequences available. We conduct exome-wide associations of single variants and rare predicted loss-of-function (pLOF) variants with CT-based hepatic fat and perform cross-modality replication in the UK Biobank (UKB) by linking whole-exome sequences to MRI-based hepatic fat. We confirm single variants previously associated with hepatic fat and identify several additional variants, including two (FGD5 H600Y and CITED2 S198_G199del) that replicated in UKB. A burden of rare pLOF variants in LMF2 is associated with increased hepatic fat and replicates in UKB. Quantitative phenotypes generated from clinical imaging studies and intersected with genomic data in medical biobanks have the potential to identify molecular pathways associated with human traits and disease.
Single-cell transcriptomic and spatial landscapes of the developing human pancreas
Authors: Oladapo Edward Olaniru, Ulrich Kadolsky, Shichina Kannambath, Heli Vaikkinen, Kathy Fung, Pawan Dhami, Shanta J. Persaud
Journal: Cell Metabolism (2022)

Current differentiation protocols have not been successful in reproducibly generating fully functional human beta cells in vitro, partly due to incomplete understanding of human pancreas development. Here, we present detailed transcriptomic analysis of the various cell types of the developing human pancreas, including their spatial gene patterns. We integrated single-cell RNA sequencing with spatial transcriptomics at multiple developmental time points and revealed distinct temporal-spatial gene cascades. Cell trajectory inference identified endocrine progenitor populations and branch-specific genes as the progenitors differentiate toward alpha or beta cells. Spatial differentiation trajectories indicated that Schwann cells are spatially co-located with endocrine progenitors, and cell-cell connectivity analysis predicted that they may interact via L1CAM-EPHB2 signaling. Our integrated approach enabled us to identify heterogeneity and multiple lineage dynamics within the mesenchyme, showing that it contributed to the exocrine acinar cell state. Finally, we have generated an interactive web resource for investigating human pancreas development for the research community.
Correlations between complex human phenotypes vary by genetic background, gender, and environment
Authors: Michael Elgart, Matthew O. Goodman, Carmen Isasi, Han Chen, Alanna C. Morrison, Paul S. de Vries, Huichun Xu, Ani W. Manichaikul, Xiuqing Guo, Nora Franceschini, Bruce M. Psaty, Stephen S. Rich, Jerome I. Rotter, Donald M. Lloyd-Jones, Myriam Fornage, Adolfo Correa, Nancy L. Heard-Costa, Ramachandran S. Vasan, Ryan Hernandez, Robert C. Kaplan, Susan Redline, Tamar Sofer
Journal: Cell Reports Medicine (2022)
Single-cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors
Authors: Shoiab Bukhari, Brian S. Henick, Robert J. Winchester, Shalom Lerrer, Kieran Adam, Yevgeniya Gartshteyn, Rohan Maniar, Ziyan Lin, Alireza Khodadadi-Jamayran, Aristotelis Tsirigos, Mary M. Salvatore, Galina G. Lagos, Steven L. Reiner, Matthew C. Dallos, Matthen Mathew, Naiyer A. Rizvi, Adam Mor
Journal: Cell Reports Medicine (2022)

PD-1 is an inhibitory receptor in T cells, and antibodies that block its interaction with ligands augment anti-tumor immune responses. The clinical potential of these agents is limited by the fact that half of all patients develop immune-related adverse events (irAEs). To generate insights into the cellular changes that occur during anti-PD-1 treatment, we performed single-cell RNA sequencing of circulating T cells collected from patients with cancer. Using the K-nearest-neighbor-based network graph-drawing layout, we show the involvement of distinctive genes and subpopulations of T cells. We identify that at baseline, patients with arthritis have fewer CD8 T
The tumor therapeutic potential of long non-coding RNA delivery and targeting
Authors: Shuo Han, Xinru Chen, Leaf Huang
Journal: Acta Pharmaceutica Sinica B (2022)

Long non-coding RNAs (lncRNAs) is a type of RNA over 200 nt long without any protein coding ability, which has been investigated relating to crucial biological function in cells. There are many key lncRNAs in tumor/normal cells that serve as a biological marker or a new target for tumor treatment. However, compared to some small non-coding RNA, lncRNA-based drugs are limited in clinical application. Different from other non-coding RNA, like microRNAs, most lncRNAs have a high molecular weight and conserved secondary structure, making the delivery of lncRNAs more complex than the small non-coding RNAs. Considering that lncRNAs constitute the most abundant part of the mammalian genome, it is critical to further explore lncRNA delivery and the subsequent functional studies for potential clinical application. In this review, we will discuss the function and mechanism of lncRNAs in diseases, especially cancer, and different approaches for lncRNA transfection using multiple biomaterials.
Co‐Polymer Carrier with Dual Advantages of Cartilage‐Penetrating and Targeting Improves Delivery and Efficacy of MicroRNA Treatment of Osteoarthritis
Authors: Yipu Zhao, Xudong Deng, Shenxing Tan, Jie Zhang, Jiangfan Han, Xue Wang, Jiawei Pei, Hui Li, Xiaoni Deng, Chong Yin, Dachuan Yin, Ye Tian, Airong Qian
Journal: Advanced Healthcare Materials (2022)

Abstract Osteoarthritis (OA) is a debilitating joint disease affecting nearly 400 million people with no efficient etiological therapies. OA is primarily identified by cartilage destruction, and gradual degeneration of the whole joint would happen when the OA progresses. Hence, cartilage has been identified as the primary therapeutic target of OA. Unfortunately, numerous barriers block the delivery of therapeutic agents into cartilage, including avascular traits and high hardness of the extracellular matrix. Herein, a cartilage‐targeting peptide (CAP) modified polyvinylamine (PVAm)‐ poly (lactic‐co‐glycolic acid) (PLGA) copolymer (CAP‐PVAm‐PLGA) is designed, which can form spherical nanoparticles with the r‐miR‐140 (CPP‐NPs). CPP‐NPs possessed enhanced mechanical properties due to the introduction of PLGA to vehicles. Meanwhile, CAP endowed the cartilage targeting which facilitated CPP‐NPs localization in cartilage. With such dual advantages, CPP‐NPs exhibited outstanding penetrability and accumulation in cartilage even subchondral bone, and can penetrate to a depth of 1000 µm into human cartilage. The degeneration area of cartilage is reduced by 65% and synovial inflammation score by 80% in OA mice, and the microarchitecture of subchondral bone is also ameliorated. These studies established a promising platform for therapeutic RNA delivery in OA therapy that overcame the cartilage barriers.
Retinopathy During the First 5 Years of Type 1 Diabetes and Subsequent Risk of Advanced Retinopathy
Authors: John I. Malone, Xiaoyu Gao, Gayle M. Lorenzi, Philip Raskin, Neil H. White, Dean P. Hainsworth, Arup Das, William Tamborlane, Amisha Wallia, Lloyd P. Aiello, Ionut Bebu
Journal: Diabetes Care (2022)

To determine whether individuals with type 1 diabetes (T1D) who develop any retinopathy at any time prior to 5 years of diabetes duration have an increased subsequent risk for further progression of retinopathy or onset of proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), diabetes-related retinal photocoagulation, or anti-vascular endothelial growth factor injections. Additionally, to determine the influence of HbA1c and other risk factors in these individuals.